Overexpression of NELFE contributes to gastric cancer progression via Wnt/β-catenin signaling-mediated activation of CSNK2B expression.
Overexpression of NELFE contributes to gastric cancer progression via Wnt/β-catenin signaling-mediated activation of CSNK2B expression.
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NELFE 的过度表达通过 Wnt/β-连环蛋白信号介导的 CSNK2B 表达激活促进胃癌进展
DOI：
10.1186/s13046-021-01848-3
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发表时间：
2021-02-01
期刊：
影响因子：
--
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Yu S;Li L;Cai H;He B;Gao Y;Li Y
背景越来越多的证据表明负延伸因子复合体成员E（NELFE）在肿瘤发生中的重要性。然而，NELFE和胃癌（GC）之间的关系仍不清楚。本研究旨在探讨NELFE在胃癌组织中的表达模式及其特异性功能。CCK-8法、集落形成法、transwell法和裸鼠模型检测细胞增殖、迁移和侵袭能力。通过生物信息学分析寻找NELFE的潜在靶基因，并利用分子生物学10-Pathway Reporter Array研究NELFE调控的信号通路。进行双荧光素酶报告基因测定、qRT-PCR和蛋白质印迹以验证它们的调控关系。结果NELFE在胃癌组织中的蛋白和mRNA表达水平均明显高于正常对照组，且与胃癌患者的预后呈负相关。功能获得和丧失实验表明，NELFE在体外和体内增强GC细胞增殖和转移。CSNK 2B被鉴定为NELFE的下游效应子。Wnt/β-catenin信号传导可能介导NELFE对CSNK 2B的调节。NELFE、β-catenin和CSNK 2B在胃癌组织中的表达均显著高于癌旁正常组织，且三者在胃癌组织中的表达水平呈正相关。
BackgroundAccumulating evidence has highlighted the importance of negative elongation factor complex member E (NELFE) in tumorigenesis. However, the relationship between NELFE and gastric cancer (GC) remains unclear. This study aimed to explore the expression pattern and specific function of NELFE in GC.MethodsNELFE expression was evaluated by immunohistochemistry and qRT-PCR in GC tissues, respectively. Cell proliferation, migration and invasion were measured by CCK-8, colony formation, transwell assays, and nude mice model. Bioinformatics analysis was performed to search potential target genes of NELFE, and a Cignal Finder 10-Pathway Reporter Array was used to explore potential signaling pathways regulated by NELFE. Dual-luciferase reporter assays, qRT-PCR and western blotting were conducted to verify their regulatory relationship. The expression correlations among NELFE, β-catenin and CSNK2B were further explored by immunohistochemistry on consecutive resections.ResultsNELFE was significantly overexpressed in GC tissues both in protein and mRNA level and negatively correlated with the prognosis of GC patients. Gain- and loss-of-function experiments showed that NELFE potentiated GC cell proliferation and metastasis in vitro and in vivo. CSNK2B was identified as a downstream effector of NELFE. Wnt/β-catenin signaling may mediate the regulation of CSNK2B by NELFE. In addition, NELFE, β-catenin and CSNK2B were all remarkably upregulated in tumor tissues compared with adjacent normal tissues, and their expression levels in GC were positively correlated with each other.ConclusionOur findings reveal a new NELFE-Wnt/β-catenin-CSNK2B axis to promote GC progression and provide new candidate targets against this disease.
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